Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.
Int J Mol Sci. 2021 Jul 23;22(15):7884. doi: 10.3390/ijms22157884.
Breast cancer is the most frequent and lethal tumor in women and finding the best therapeutic strategy for each patient is an important challenge. PARP inhibitors (PARPis) are the first, clinically approved drugs designed to exploit synthetic lethality in tumors harboring mutations. Recent evidence indicates that PARPis have the potential to be used both in monotherapy and combination strategies in breast cancer treatment. In this review, we show the mechanism of action of PARPis and discuss the latest clinical applications in different breast cancer treatment settings, including the use as neoadjuvant and adjuvant approaches. Furthermore, as a class, PARPis show many similarities but also certain critical differences which can have essential clinical implications. Finally, we report the current knowledge about the resistance mechanisms to PARPis. A systematic PubMed search, using the entry terms "PARP inhibitors" and "breast cancer", was performed to identify all published clinical trials (Phase I-II-III) and ongoing trials (ClinicalTrials.gov), that have been reported and discussed in this review.
乳腺癌是女性中最常见和最致命的肿瘤，为每位患者找到最佳治疗策略是一个重要的挑战。PARP 抑制剂（PARPi）是第一种经临床批准的旨在利用携带有害突变的肿瘤中的合成致死性的药物。最近的证据表明，PARPi 有可能在乳腺癌治疗中单独使用或联合使用。在这篇综述中，我们展示了 PARPi 的作用机制，并讨论了它们在不同乳腺癌治疗环境中的最新临床应用，包括作为新辅助和辅助治疗的应用。此外，作为一类药物，PARPi 具有许多相似之处，但也存在一些关键差异，这些差异可能具有重要的临床意义。最后，我们报告了目前关于 PARPi 耐药机制的知识。通过系统的 PubMed 搜索，使用“PARP 抑制剂”和“乳腺癌”这两个检索词，我们确定了所有已发表的临床试验（I 期-II 期-III 期）和正在进行的试验（ClinicalTrials.gov），这些试验都在本综述中进行了报道和讨论。
